Gene knock-out mouse models have become gold standards for delineating molecular and functional roles of specific genes. In an attempt to generate such models for neurological disorders, we have initiated studies to disrupt the apolipoprotein D (ApoD) gene in mouse embryonic stem cells. We have used rat ApoD cDNA probe to screen the 129/svj mouse genomic library. Eight genomic clones of ApoD have been isolated and characterized. An ApoD targeting construct has been engineered for positive/negative selection. ApoD cDNA has been cloned by RT-PCR from mouse kidney RNA. We expect to produce an ApoD knock-out mouse in the near future in order to determine the role of ApoD in nerve regeneration as well as its potential role in breast and prostate cancer.